The cytotoxic properties of human lymphocytes activated in mixed cell cultures with allogeneic lymphocytes or LCL cells have been investigated. Both activation and cytotoxic reactions could be obtained with almost pure populations of lymphocytes. No supernatant factors appeared to be involved. Human thymocytes and blood lymphocytes from pigs, guinea-pigs or rabbits were ineffective. Fibroblasts from human skin were not effective activators of human blood lymphocytes. There were marked differences in the susceptibility of various target cells to the cytotoxic reaction which could not be accounted for by any known antigenic classification. Various LCL cells were shown to lack cytotoxic potential under a variety of experimental conditions and, by this criterion, lacked immunological competence. It is suggested that the growth of abnormal lymphoid cells in vivo may be prevented by the cytotoxic mechanism described.